Physical and Biological Treatment Strategies to Prevent Post-Traumatic Joint Contracture

预防创伤后关节挛缩的物理和生物治疗策略

• 批准号: 10374002
• 负责人: Spencer Park Lake
• 金额: $ 33.21万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10374002
• 关键词: Affect; Animal Model; Animals; Articular Range of Motion; Biological; Biological Response Modifier Therapy; Biology; Cell Proliferation; Cellularity; Clinical; Collagen; Combined Modality Therapy; Connective Tissue; Contracts; Contracture; Deposition; Dislocations; Dose; Drug usage; Elbow; Elbow Injury; Elbow joint structure; Engineering; Etiology; Evaluation; Exercise; Exhibits; Extracellular Matrix; Fibrosis; Fracture; Functional disorder; Gait; Health Promotion; Human; Hypertension; Hypertrophy; Immobilization; Impairment; Injury; Interdisciplinary Study; Intervention; Joint Dislocation; Joints; Lead; Losartan; Mechanics; Minor; Modeling; Motion; Operative Surgical Procedures; Pain; Pathology; Patients; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Physical Rehabilitation; Physical therapy; Predisposition; Prevention; Prevention strategy; Preventive treatment; Production; Profibrotic signal; Pronation; Property; Protocols documentation; Quantitative Evaluations; Rattus; Rehabilitation therapy; Residual state; Severities; Simvastatin; Supination; System; Time; Tissue Preservation; Tissues; Treatment Protocols; Work; capsule; clinically relevant; design; disability; experience; gait symmetry; hypercholesterolemia; innovation; joint function; post-traumatic symptoms; preservation; prevent; reduce symptoms; response; standard care; tool; treadmill; treatment strategy

PROJECT SUMMARY Post-traumatic joint contracture (PTJC) often leads to debilitating impairment following injury, especially in the elbow where even minor injuries can lead to drastic disability. PTJC is a challenging clinical condition that is difficult to reverse, so preventative treatment strategies are urgently needed. Mechanisms governing successful physical therapy are poorly understood; systematic evaluation is needed to determine the potential of physical rehabilitation. Several drugs have demonstrated anti-fibrotic effects in other systems; focused studies are needed to evaluate if biological therapy using these drugs is able to reduce PTJC. Also, the potential synergistic impact of combined physical/biological therapies is unknown. The objective of this study is to utilize a validated animal model of PTJC to investigate physical and biological strategies to preserve mechanics/function (e.g., range of motion and gait patterns) of the elbow joint following injury. SA1: Determine if physical treatments can prevent PTJC and preserve mechanics/function of injured elbows. We will identify whether active motion is successful in reducing PTJC, and determine which governing principles best preserve joint mechanics. Hypothesis: Low-intensity, long-duration physical therapy will be most effective at preserving joint mechanics and function by reducing excessive ECM deposition and tissue fibrosis, while also limiting potential joint wear from high-intensity therapy. SA2: Determine if biological treatments can prevent PTJC and preserve mechanics/function of injured elbows. We will investigate whether the pleiotropic anti- fibrotic effects of simvastatin and losartan can prevent PTJC and identify which treatment protocol best preserves joint mechanics/function. Hypothesis: Both simvastatin and losartan will reduce PTJC severity but a combination of low doses of both drugs will be most effective in preserving joint mechanics and function by reducing the fibrotic response in joint tissues, especially by limiting post-traumatic collagen production. SA3: Determine if synergistic and/or compensatory effects of a combined physical-biological treatment strategy can maintain elbow joint mechanics/function at pre-injury levels. We will investigate the degree to which a well-designed physical therapy protocol (from Aim 1) combined with strategic biological intervention (from Aim 2) can eliminate symptoms of PTJC. Hypothesis: Treatment aimed at both limiting the fibrotic biological response via drug therapy and disrupting fibrosis via physical therapy will be most effective in preserving joint mechanics/function by limiting tissue fibrosis due to synergistic and compensatory benefits of combined therapy. Successful completion of this study will elucidate treatment principles that best prevent contracture and dysfunction after injury via clinically-available physical, biological, and/or combined treatment strategies. Results will be impactful for understanding etiology and pathophysiology in other articulating joints that are susceptible to contracture. This study will leverage an interdisciplinary research team to quantify the mechanical, biological, and functional aspects of PTJC prevention using tools of engineering and biology.

项目总结

项目成果

Investigating the Effects of Physical Therapy Timing, Intensity and Duration on Post-Traumatic Joint Contracture in a Rat Elbow Model.

• DOI: 10.32098/mltj.03.2021.20
• 发表时间: 2021-07
• 期刊: Muscles, ligaments and tendons journal
• 作者: Reiter AJ;Castile RM;Schott HR;Kivitz GJ;Chamberlain AM;Lake SP
• 通讯作者: Lake SP

Pleiotropic Effects of Simvastatin and Losartan in Preclinical Models of Post-Traumatic Elbow Contracture.

• DOI: 10.3389/fbioe.2022.803403
• 发表时间: 2022
• 期刊: Frontiers in bioengineering and biotechnology
• 影响因子: 5.7
• 作者: David MA;Reiter AJ;Dunham CL;Castile RM;Abraham JA;Iannucci LE;Shah ID;Havlioglu N;Chamberlain AM;Lake SP
• 通讯作者: Lake SP

Females and males exhibit similar functional, mechanical, and morphological outcomes in a rat model of posttraumatic elbow contracture.

• DOI: 10.1002/jor.24918
• 发表时间: 2021-09
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Reiter AJ;Schott HR;Castile RM;Cannon PC;Havlioglu N;Chamberlain AM;Lake SP
• 通讯作者: Lake SP

Early Joint Use Following Elbow Dislocation Limits Range-of-Motion Loss and Tissue Pathology in Posttraumatic Joint Contracture.

• DOI: 10.2106/jbjs.22.00064
• 发表时间: 2023-02-01
• 期刊: The Journal of bone and joint surgery. American volume